The University of Louisville (UofL) Hepatobiology and Toxicology COBRE is a unique thematic research center. The UofL COBRE scientists comprise a multidisciplinary group senior mentors and junior investigators focusing on the mechanisms and therapy for liver injury, nutrition and gut:liver interactions, and liver:environment/toxin/dru interactions. The liver is the largest internal organ in the body, and is possibly the most complex organ in terms of metabolism. Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) is the most common liver disease, affecting about 1/3 of adults and over 10% of children in the US. NAFLD arises most commonly among overweight/obese individuals, and is highly linked to the Metabolic Syndrome. Alcoholic Liver Disease (ALD) remains a common problem among those who drink. Environmental Toxicant Induced Liver Injury is an increasingly recognized problem, and Louisville has been a leader in this area. Hepatitis B and C remain important causes of cirrhosis and hepatocellular carcinoma (HCC) worldwide. Personalized Medicine is an increasingly important factor in medication efficacy. Drug-Induced Liver Injury (DILI) is the most common reason drugs are removed from the market and an important cause of liver failure. This COBRE brings together experienced senior mentors and promising junior investigators from across UofL in collaboration with scientists across the U.S./World to perform cross-cutting research on the unique topics of Hepatobiology and Toxicology. The Specific Aims of the Hepatobiology and Toxicology COBRE are to: 1. Develop a thematically-focused program in Hepatobiology and Toxicology that strengthens the overall research infrastructure at UofL. 2. Create a multidisciplinary program in research education, mentoring and career development in Hepatobiology and Toxicology. 3. Provide the necessary research resources and translational science/basic technologies to support and sustain state-of-the-art research in Hepatobiology and Toxicology. 4. Discover new mechanisms/molecular targets and effective means for preventing and/or treating liver diseases/toxicant exposures and communicate our findings to the public.